IT202100011750A1 - FORMULATION FOR ROSACEA ACNE - Google Patents

Description

FORMULATION FOR ROSACEA ACNE

FIELD OF THE INVENTION

The present invention refers to a composition comprising nicotinamide, zinc, copper and reduced glutathione (GSH), to offer relief from the unpleasant sensations typical of hypersensitive skin, protecting the skin barrier and soothing irritations, helping to balance sebum secretion, improve the cellular metabolism, increasing the permeability? of the skin. The present invention also relates to said compositions for use in the treatment of rosacea and its symptoms.

STATE OF THE ART

Rosacea acne ? a chronic inflammatory skin disease, which mainly affects adults, with light complexion and hair (for this reason it is also known as the "Celtic Curse"). The onset of dermatological pathology? accompanied by redness located mainly on the cheeks, nose, chin and forehead. Rosacea tends to have a progressive course, so the symptoms tend to get worse over time: the redness tends to increase until it becomes persistent. If not treated properly, acne rosacea can give rise to skin lesions, swelling of the nose and also affect the region around the eyes (ocular rosacea). For some subjects, the course of rosacea ? cyclical: symptoms may flare up for a limited period of a few weeks or months, and then decrease before worsening again. Rosacea acne ? a primarily vascular disorder: the early disorders are the typical redness, due to alterations of the venous flows; the first lesions in the skin are pathological dilations of the blood capillaries.

There is no actual therapy dedicated to the treatment of acne rosacea, but the treatment can? relieve symptoms and control their progression. The dermatologist (specialist for skin diseases) can recommend the most appropriate medical treatment regimen? appropriate, as well as recommending certain moisturizers, mild cleansers, sunscreens, and other products to improve skin health.

There are several options for treating rosacea. You may need a combination of topically applied (lotion, cream, or gel) and orally (pills, capsules, or tablets) medications. The duration of treatment depends on the type and severity of of the symptoms. Often, ? long-term therapy is needed to prevent symptoms from recurring.

Since the most common drugs have not yet been identified? indicated for the complete cure of the disease, the substances listed below are not useful for healing; rather, such treatments are aimed at improving the person's aesthetic appearance, as well as reducing any inflammation associated with rosacea.

The drugs for acne rosacea to be applied locally, have an activity? antibacterial and anti-inflammatory: These include antibiotics, such as metronidazole, tetracycline, erythromycin, sodium sulfur disulfacetamide or azelaic acid, topical retinoids, such as isotretinoin, or corticosteroids, such as loteprednol; and can be included in maintenance treatment programs for symptom control. These topical applications can also lead to side effects such as skin irritation, redness, dry skin or burning skin.

Even Nature offers some useful remedies for the treatment of rosacea: some products specifically formulated to treat rosacea are available in herbal medicine, such as artichoke, chicory, walnut, rosemary, butcher's broom and vine. These natural remedies act on the microcirculation, increasing the resistance of the capillaries, counteracting their fragility, a typical feature of rosacea.

In the state of the art ? therefore the problem of providing methods and compositions capable of treating this pathology and alleviating its symptoms such as: acne, redness of the face (forehead, nose, cheeks), formation of telangiectasias on the face, red eyes, tendency to tear and redness and prickling sensation sometimes associated with itching, resulting from acne rosacea.

SUMMARY OF THE INVENTION

The technical problem posed and solved by the present invention ? is to provide natural anti-inflammatory composition for acne rosacea can improve facial microcirculation, balance sebum secretion, improve cell metabolism, increase skin permeability of the skin, and quickly eliminate the inflammation of the skin.

This problem is solved by the use of a composition comprising nicotinamide, zinc, copper and reduced glutathione (GSH) according to claim 1.

The association of nicotinamide with glutathione makes it possible to maintain adequate glutathione levels even during the inflammatory stress of acne rosacea.

NADPH oxidase inhibitors such as zinc therefore have a protective influence taking into account the decrease of ROS formation.

Copper, at the intracellular level, participates together with glutathione in reducing the oxidative stress at the base of acne rosacea. To achieve the long-lasting and appropriate intracellular effect of copper and glutathione, ? necessary to supply glutathione with nicotinamide, which ensures the regeneration of glutathione in a reduced form. Zinc acts downstream, in turn promoting the formation of reduced nicotinamide, which will act as a substrate to form reduced glutathione, which in turn acts in synergy with copper to reduce ROS but also to allow the latter to enter the cell.

Preferred features of the present invention are the subject of the dependent claims.

? further object of the present invention is a cosmetic product comprising or consisting of the composition according to any of the embodiments described herein in the form of serums, face masks, make-up remover wipes, cleansing wipes, moisturizing creams, lifting creams, moisturizing gels, make-up removers, exfoliants, tonics, micellar waters and/or make-up products.

In the end, ? further object of the present invention said composition for use in the treatment of acne rosacea, in particular to prevent, reduce and/or eliminate symptoms caused by acne rosacea and/or flushing and/or couperouge and/or fragility? capillaries and/or telangiectasias and/or localized pustulosis of the face.

DETAILED DESCRIPTION

The present invention relates to a composition comprising nicotinamide, zinc, copper and intracellular glutathione (GSH).

Nicotinamide (the amide form of vitamin B3)? It has been used in dermatology for over 40 years for a wide range of conditions including acne, rosacea, autoimmune bullous dermatoses and now the treatment and prevention of photoaging and photoimmunosuppression.

The broad clinical effects of nicotinamide can be explained by its role as a cellular energy precursor, modulator of inflammatory cytokines, and inhibitor of the nuclear enzyme poly(adenosine diphosphate-ribose) polymerase-1, which plays a significant role in DNA repair, maintenance of stability? genomics and cellular response to injury, including inflammation and apoptosis. Its use in rosacea is mainly due to its activities? anti-inflammatory.

According to research carried out in recent years, zinc has the same properties of antibiotics, such as tetracycline and pu? fight acne bacteria efficiently, not showing the negative effects of antibiotics and improving immunity of the body. Also, zinc? fundamental in the keratinization process, i.e. in the correct regulation of the maturation of keratin, which is dysregulated in the course of acne rosacea.

Zn<2+ > ions reduce the production of reactive oxygen species (ROS) by inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The list of ROS, affected by Zn<2+> production, includes oxygen-based molecules comprising superoxide anion radical (?O2?), hydrogen peroxide (H2O2) and hydroxyl radicals (?OH), which are by-products of cellular metabolism. However, at high concentrations, they can cause alterations in various molecules and damage cellular structures; NADPH oxidase inhibitors such as zinc could therefore have a protective influence taking into account the decrease of ROS formation.

Copper ? a trace element essential for normal activity mobile phone. In fact, it acts as a cofactor for numerous enzymes, involved in various activities? metabolic: in the protection from oxidative stress, re-entering the structure of Superoxide dismutase and Ceruloplasmin; in the formation of the connective tissue, participating in the activity? of the enzyme lysyl oxidase; in the synthesis of melanin, participating in the activity? of cuproenzyme tyrosinase, which is necessary for the formation of the pigment melanin (which plays a role in the pigmentation of hair, skin and eyes). The activity coenzymatic action of copper against enzymes such as lysyl oxidase guarantees correct synthesis and branching of the connective tissue, optimizing the formation of cross-linking between collagen fibres, and thus structuring the structure of the connective tissue. the matrix. Would copper be able, with mechanisms that are not yet fully understood, to control the activity? of the cells responsible for the first response against potential pathogens, guaranteeing an enhancement of the activity? engulfing neutrophils and monocytes and providing effective protection against harmful agents of various kinds. In the skin, copper performs a plethora of activities different, essential for the performance of physiological functions. Indeed, it stimulates the proliferation of dermal fibroblasts, upregulates the production of collagen (types I, II and V) and elastin fibers (elastin, fibrillins) by fibroblasts, apparently through the induction of TGF-?, stimulates HSp- 47, essential for the formation of collagen fibrils, acts as a cofactor of LOX necessary for effective cross-linking of extracellular matrix proteins, since the increase in cross-linking of collagen and elastin matrices occurs in a copper dose-dependent manner.

However, in order to carry out the activities? copper must be correctly transported at the intracellular level. The absorption of copper ? dependent on glutathione concentrations, which, as seen previously, tend to decrease in inflammatory states. Therefore, to favor a correct entry into the copper cell, ? it is essential to associate it with glutathione, without which copper could not reach an efficient concentration in the inflammatory states of acne rosacea. Furthermore, as previously mentioned, the redox state ? the basis of inflammation, and the association between nicotinamide and glutathione favors the reduction of ROS production. Copper also intervenes in the regulation of the redox state being a cofactor of superoxide dismutase, an antioxidant enzyme present in the skin, important for the protection against free radicals and above all it inhibits cellular oxidative effects such as membrane damage and lipid peroxidation. Therefore, the rationale for combining copper with glutathione and nicotinamide?:

- copper, to enter the cell, needs a sufficient quantity? of glutathione, which is reduced in inflammatory states;

- copper, at the intracellular level, participates together with glutathione in reducing the oxidative stress at the base of acne rosacea;

- to achieve the long-lasting and appropriate intracellular effect of copper and glutathione, ? It is necessary to supply glutathione with nicotinamide, which ensures the regeneration of glutathione in a reduced form, allowing both to act on the ROS and to remain at concentrations such as to favor the absorption of copper.

- zinc acts downstream, in turn favoring the formation of reduced nicotinamide, which will act? as a substrate to form reduced glutathione, which in turn acts in synergy with copper to reduce ROS but also to allow the latter to enter the cell.

Intracellular glutathione (GSH) ? the main scavenger protection mechanism against increased oxidative stress. ? been described a

GSH metabolism impaired in rosacea.

Chronic inflammation, such as rosacea, is associated with oxidative stress. Oxidative stress occurs when the amount of reactive oxygen species (ROS) exceeds the capacity? buffer of the endogenous antioxidant defense system. Several studies have shown that oxidative stress is strongly involved in the pathogenesis of rosacea. In skin biopsies from patients with rosacea, ROS levels are higher higher than healthy controls. Individuals with rosacea have increased levels of ROS and decreased levels of antioxidants such as ascorbic acid also in the blood. UV radiation, a well-known trigger and aggravator of rosacea, is a potent inducer of ROS formation in the skin. ROS are mediators of cytokine induction in human keratinocytes. Glutathione (GSH), a tripeptide made up of L-glutamate, cysteine and glycine, is the low molecular weight thiol pi? abundant in animal cells. The GSH? present in millimolar concentrations in virtually all normal cells; Therefore, the GSH ? the major intracellular antioxidant buffer against oxidative stress and exists primarily in the forms of reduced glutathione (GSH) and oxidized glutathione (GSSG). For these reasons, therapeutic strategies aimed at increasing intracellular GSH levels could be, at least theoretically, an interesting tool to contrast the pathogenetic role of oxidative stress in rosacea. However, the GSH has a capacity? very low to cross the cell membrane. The intracellular levels of GSH are, in fact, mainly the result of internal synthesis. Nicotinamide plays a fundamental role in the correct maturation of the skin, preventing damage caused by external factors. At the same time, nicotinamide intervenes in the redox balance of the cell, i.e. it balances the intracellular oxidation and reduction reactions. Indeed, a correct level of nicotinamide ? essential in the continuation of the activities? of reduction and oxidation which occurs above all in inflammatory states. In particular, the nicotinamide ? able to promote the regeneration of reduced glutathione, one of the main protagonists in the inflammatory balance. Now, why? the glutathione ? one of the main elements involved in the regulation of inflammation in cells, and because it? does rosacea have a conspicuous inflammatory component, yes? since the intracellular reduced glutathione tends to decrease considerably, with an imbalance that tends in favor of inflammation. Keeping glutathione levels high in inflammatory diseases? fundamental. Therefore, the association of nicotinamide with glutathione makes it possible to maintain adequate glutathione levels even during the inflammatory stress of acne rosacea. The ingredients described up to now represent, in an embodiment of the present invention, the main active ingredients.

The active ingredient? defined as the substance that possesses a certain activity? biological, therefore, all substances with a therapeutic effect such as drugs or beneficial such as vitamins and probiotics.

In one embodiment of the present invention, according to any of the embodiments described herein, the composition may further understand one or more? of the following substances: Vitamin C, Vitamin E, Papain, Acid-18-?-glycyrrhetic, Hyaluronic Acid.

Vitamin C (or ascorbic acid) ? the vitamin par excellence, as it participates in numerous biological processes and "protective" physiological mechanisms for the organism. Normal skin contains high concentrations of vitamin C, which supports important and well-known functions by stimulating collagen synthesis and aiding in antioxidant protection against UV-induced photodamage. In the cosmetic field, vitamin C? known above all for its powerful activity? antioxidant. This is expressed through the scavenger effect, that is? it literally behaves like a "scavenger" of reactive oxygen species and participates in the regeneration of ?-tocopherol (vitamin E), starting from its oxidized form. On the one hand, therefore, vitamin C ? capable of providing direct anti-radical protection (reduces chemical reactivity and, consequently, the toxicity of free radicals); on the other, ? able to amplify the benefits ensured by other antioxidant substances (including vitamin E) and participates in the metabolic processes that lead to their physiological regeneration, making them useful again in their important activity. against free radicals. Also, vitamin C ? essential to maintain the? integrity? of the collagen fibers of the vessels, fortifying them, and acting on one of the main causes of rosacea.

Vitamin E? an important fat-soluble antioxidant and ? in use by pi? 50 year old in dermatology. ? an important ingredient in many cosmetic products.

It protects the skin from various deleterious effects due to solar radiation by acting as a free radical scavenger. Experimental studies suggest that vitamin E has properties mitostatic and photoprotective. In one of the studies conducted on 98 patients suffering from acne rosacea, ? been obtained with a compound of vitamin E and vitamin C ? been obtained the control of defective keratinization, thus depriving? the Propionibacterium acnes of the substrate necessary for growth. Vitamin E prevents bacterial induced lipid peroxidation in the follicles and within the sebaceous glands, thus preventing fat burning. inflammation due to peroxide irritation.

The papain? a proteolytic enzyme present in papaya juice (Carica papaya). The results showed that papain achieves its exfoliating effect by acting on the extracellular junctions that hold keratinocytes together. This facilitates the exfoliation of the superficial layers of the skin allowing greater penetration of the other active ingredients without increasing inflammation.

A highly active plant ingredient ? 18?-glycyrrhetinic acid (GA), the major metabolite of glycyrrhizin (GL), obtained from licorice root. GA shows activity? anti-inflammatory by suppressing the expression of proinflammatory genes, inhibiting the production of inflammatory cytokines and influencing the transformation of arachidonic acid into pro-inflammatory leukotrienes. Also, GA has properties antioxidants and this activity? ? directed to the inactivation of free radicals and the inhibition of lipid oxidation. GA shows low toxicity against normal human cell lines, fibroblasts and keratinocytes. Its substantial activity? antimicrobial against some strains of bacteria indicates that GA could be the promising candidate for the treatment of microbe-induced diseases and skin disorders.

Hyaluronic acid? a simple linear polymer in which a simple disaccharide is repeated thousands of times, thus creating a huge hydrophilic molecule that imparts a large volume of hydration and contributes to turgidity and flexibility. of healthy skin. A thorough review of the literature revealed that HA formulations (i.e. gels, creams, intradermal filler injections, dermal fillers, facial fillers, autologous fat gels, lotions, serums and implants, etc.) exhibit remarkable properties ? anti-aging, with pumpling effect, fillers and rejuvenates the face. Furthermore, hyaluronic acid also performs anti-inflammatory.

In a preferred embodiment of the present invention, the composition comprises: Hyaluronic Acid; Nicotinamide; papain; Copper; Zinc; Glutathione; C vitamin; 18-?- Glycyrrhetinic acid and Vitamin E.

The concentration range of the active principle of hyaluronic acid present in the compositions described here can vary from 0.01% to 0.2%, preferably ? equal to 0.1% (by weight with respect to the total weight of the composition).

As regards the concentration of the active ingredient of Nicotinamide, the range described can ranging from 0.01% to 0.5%, preferably 0.4% (by weight with respect to the total weight of the composition).

With reference to the Papain concentration in the compositions described in the present invention, the range ? between 0.01% and 0.2%, with the preferred concentration fixed at 0.1% (by weight with respect to the total weight of the composition).

Furthermore, the concentration of copper present can be between 0.01% and 0.5%, preferably ? equal to 0.2% (by weight with respect to the total weight of the composition).

The concentration of Zinc present in any of the embodiments described in the present invention varies from 0.01% to 0.3%, with a preferential value of 0.1% (by weight with respect to the total weight of the composition).

As regards the concentration of the active principle of reduced glutathione (GSH), the values can vary from 0.01% to 0.3%, preferably ? equal to 0.1% (by weight with respect to the total weight of the composition).

Considering the concentration values of Vitamin C, they can range from 0.01% to 0.3%, preferably ? equal to 0.1% (by weight with respect to the total weight of the composition).

The concentration of 18-?-glycyrrhetic acid within the described compositions varies from 0.01% to 0.5%, with a preferential value of 0.2% (by weight with respect to the total weight of the composition).

Finally, the concentration value referred to Vitamin E, ? present in a range between 0.01% and l?1%, preferably ? equal to 0.7% (by weight with respect to the total weight of the composition).

Advantageously, in order to broaden the spectrum of protection provided by the present invention, Sun Protection Factors (SPF) can be further included in one embodiment.

The SPF indicates which ? the degree of protection that a cosmetic product can guarantee against UV rays. It is an index expressed through a numerical value that is always found on creams: pi? ? high the number, greater ? the protection offered by ultraviolet radiation.

According to one of the embodiments of the present invention the composition will comprise: Hyaluronic acid (0.1%); Nicotinamide (0.4%); Papain (0.1%); Copper (0.2%) Zinc (0.1%); Glutathione (0.1%); Vitamin C (0.1%); 18-?-glycyrrhetic acid (0.2%); Vitamin E (0.7%); SPF filters; (percentages understood as weight of the component compared to the total weight of the composition).

According to one of the embodiments of the present invention, the composition is used for topical use, the composition will be? therefore preferably in the form of: cream, ointment, ointment, lotion, tonic, gel, paste, foam, hydrophobic gel, hydrophilic gel, emulsion, suspension or liquid. Depending on the type of formulation, the composition can further understand one or more? excipients and/or carriers. For lipophilic ointments, the excipients can be chosen from among: solid, semi-solid and/or liquid paraffins, vegetable oils, waxes, liquid silicones, which generally have properties occlusive or protective. ? It is also possible to add surfactants such as sorbitan esters, lanolin alcohols, fatty alcohols, fatty acid sulfates, fatty acid esters and/or polysorbates to obtain an ointment that emulsifies in water.

As regards instead the composition of the present invention in the form of a hydrophilic ointment, suitable excipients to be added will be mixtures of polyethylene glycols.

With reference to a possible embodiment in which the composition described by the present invention ? in the form of a cream, being the cream a multiphase preparation consisting of a lipophilic and a hydrophilic phase, it is the addition of emulsifiers is essential. In the case of hydrophobic creams, the emulsifiers that can be added are wool alcohols, sorbitan esters and/or monoglycerides, while with reference to hydrophilic creams, the emulsifiers will be sodium soaps, polysorbates and/or fatty alcohol sulphates.

As regards compositions formulated as hydrophilic gels, the addition of hydrophilic macromolecules, such as sodium alginate, agar-agar, gums, gelatin, starch, cellulose derivatives and/or carboxy-vinyl-polymers, is essential.

In the case of hydrophobic gel, excipients that can be included are: micronized silica, hydrogenated castor oil, stearyl-ammonium hettorite, zinc stearates, calcium stearates and/or aluminum stearates.

Other excipients can be moisturizing substances such as collagen, elastin, various protein hydrolysates, nucleic acid hydrolysates, natural moisturizing factor; or absorption promoters, such as DMSO, fatty acids, urea-azone and/or menthol. Further object of the present invention ? the development of a cosmetic product comprising or consisting of: Nicotinamide, Copper, Zinc, Glutathione and/or Vitamin C and/or 18-?-Glycyrrhetic Acid and/or Vitamin E and/or Hyaluronic Acid and/or Papain.

The cosmetic product in question, according to the present invention, can be conceived in the form of: serum, face mask, make-up remover wipe, cleansing wipe, moisturizer, lifting cream, moisturizing gel, make-up remover, exfoliator, toner, micellar water, make-up product.

All the embodiments described up to now can be prepared by any of the known methods used in the cosmetic sector.

The composition shown in this description can? be used as a medicine.

In particular, this medicine can be used in the treatment of acne rosacea, frailty? capillaries, telangiectasias and pustulosis localize on the face.

In the end, ? object of the claim is the cosmetic (non-therapeutic) use of the composition according to any of the previously described embodiments, in order to prevent, reduce and/or eliminate skin imperfections such as for example flushing and couperouge, in particular localized on the face.

The use of this composition provides for the application in the morning, after thorough cleansing and drying of the area concerned, and possibly in the evening, for a total of at least once, massaging delicately until completely absorbed.

EXAMPLES

Example 1 - Hyaluronic acid (0.1%); Nicotinamide (0.4%); Papain (0.1%); Copper (0.2%) Zinc (0.1%); Glutathione (0.1%); Vitamin C (0.1%); 18-?-glycyrrhetic acid (0.2%); Vitamin E (0.7%); with SPF filters.

Appearance: Emulsion

Green colour

Flavor: NA

Odour: Characteristic

pH: 5.5-6.5

Density: 0.95-0.99 g/ml

Refractive index: ND

Flash point: Not flammable

solubility in water: Insoluble

Claims (11)

1. Composition comprising nicotinamide, zinc, copper and intracellular glutathione (GSH). 2. The composition according to claim 1, further comprising one or more? of the following substances Vitamin E, Vitamin C, Hyaluronic acid, Papain, Acid-18 ?-glycyrrhetic. 3. The composition according to any one of claims 1 to 2, comprising: Hyaluronic acid; Nicotinamide; papain; Copper; Zinc; Glutathione; C vitamin; 18-?-glycyrrhetinic acid and Vitamin E. 4. The composition according to any one of claims 1 to 3, wherein the hyaluronic acid is present in a range between 0.01% and 0.2%, preferably 0.1%; and/or the Nicotinamide? present in a range between 0.01% and 0.5%, preferably 0.4%; and/or Papain? present in a range of 0.01% to 0.2%, preferably 0.1%; and/or in which the Copper ? present in a range between 0.01% and 0.5%, preferably 0.2%; and/or the zinc? present in a range of 0.01% to 0.3%, preferably 0.1%; and/or in which Glutathione ? present in a range of 0.01% to 0.3%, preferably 0.1%; and/or in which Vitamin C ? present in a range of 0.01% to 0.3%, preferably 0.1%; and/or in which the 18-?-glycyrrhetinic acid ? present in a range between 0.01% and 0.5%, preferably 0.2%; and/or in which Vitamin E ? present in a range between 0.01% and 1%, preferably 0.7%. The composition according to any one of claims 1 to 4, further comprising sun protection factors (SPF). 6. The composition according to any one of claims 1 to 5, for topical use. The composition according to claim 6, in the form of a cream, ointment, ointment, lotion, tonic, gel, paste, foam, hydrophobic gel, hydrophilic gel, emulsion, suspension or liquid. 8. Cosmetic product comprising or consisting of a composition according to any one of claims 1 to 7, wherein said product is in the form of a serum, face mask, makeup remover wipe, cleansing wipe, moisturizer, lifting cream, hydrating gel, makeup remover, exfoliator, toner, micellar water, make-up product. 9. Cosmetic use of the composition, according to any one of claims from 1 to 8, to prevent, reduce and/or eliminate skin blemishes, in particular flushing and/or couperouge localized on the face. 10. Composition according to any one of claims 1 to 7, as a medicament. 11. Composition according to any one of claims 1 to 7 for use in the treatment of acne rosacea, flushing, couperouge, fragility? capillaries, facial pustulosis and/or telangiectasias.